EP3377470A1 - Process for the synthesis of intermediates useful for preparing 1,3,4-triazine derivatives - Google Patents

Process for the synthesis of intermediates useful for preparing 1,3,4-triazine derivatives

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Publication number
EP3377470A1
EP3377470A1 EP16866914.1A EP16866914A EP3377470A1 EP 3377470 A1 EP3377470 A1 EP 3377470A1 EP 16866914 A EP16866914 A EP 16866914A EP 3377470 A1 EP3377470 A1 EP 3377470A1
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EP
European Patent Office
Prior art keywords
diethyl
dibromomalonate
bromomalonate
chloromalonate
dichloromalonate
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Granted
Application number
EP16866914.1A
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German (de)
French (fr)
Other versions
EP3377470B1 (en
EP3377470A4 (en
Inventor
Sheng Xu
Yihui Xu
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FMC Corp
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FMC Corp
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Publication of EP3377470A4 publication Critical patent/EP3377470A4/en
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C249/00—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton
    • C07C249/16—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton of hydrazones
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B43/00—Formation or introduction of functional groups containing nitrogen
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
    • C07C251/72—Hydrazones
    • C07C251/74—Hydrazones having doubly-bound carbon atoms of hydrazone groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C251/76—Hydrazones having doubly-bound carbon atoms of hydrazone groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of a saturated carbon skeleton

Definitions

  • the present invention relates to the synthesis of the intermediates useful for the preparation of 1,3,4- triazine derivatives, more specifically the intermediate is 1 ,3-diethyl 2-(2-methylhydrazinylidene)propanedioate.
  • 1,3,4- triazine-based derivatives are a subgroup of the triazines and many of them exhibit herbicidal activity and have been synthesized and widely used to protect crop against weeds. More recently, a novel 1,3,4-triazine based derivative was reported by SHIBAYAMA, Atsushi, et al in WO 2012/002096 A.
  • 1,3-diethyl 2-(2-methylhydrazinylidene)propanedioate (the "DMP") is an important intermediate compound for the preparation of the 1,3,4- triazine based derivatives and that is used mainly to form the 1,3,4- triazine ring.
  • the diethyl malonate is often used as a starting raw material and first converted to diethyl ketomalonate. Then, the resultant diethyl ketomalonate is to react with methylhydrazine to obtain DMP.
  • the present invention provides a novel process for the synthesis of 1,3-diethyl 2-(2- methylhydrazinylidene)propanedioate.
  • the present process uses 2-halo-substituted diethyl malonate (referred to herein as "-DEM”) and does not need convert diethyl malonate to diethyl ketomalonate. Therefore, the unwanted hazardous oxidation and complicated side reaction are avoided.
  • -DEM 2-halo-substituted diethyl malonate
  • the present invention provides a process for the synthesis of 1,3-diethyl 2-(2-methylhydrazinylidene)propanedioate by reacting 2-halo- substituted diethyl malonate with methylhydrazine or the salt thereof.
  • 2-halo-substituted diethyl malonate is selected from the group consisting of diethyl 2-bromomalonate, diethyl 2,2-dibromomalonate, diethyl 2- chloromalonate, diethyl 2,2-dichloromalonate, and any mixtures thereof.
  • the present invention provides a process for the synthesis of 1,3-diethyl 2-(2-methylhydrazinylidene)propanedioate, comprising:
  • the present invention provides a process for the preparation of 1,3-diethyl 2- (2-methylhydrazinylidene)propanedioate by using 2-halo-substituted diethyl malonate.
  • the present invention provides a process for the synthesis of 1,3-diethyl 2-(2-methylhydrazinylidene)propanedioate by reacting a 2-halo- substituted diethyl malonate with methylhydrazine or the salt thereof.
  • 2-halo-substituted diethyl malonate refers to a halo-substituted diethyl malonate that includes one or two halogen substituent(s) at carbon-2 position of the diethyl malonate.
  • the halo-substituent can be any member of the halogen family, including fluorine, bromine, chlorine, iodine and combinations thereof. In case of two halogen substituent, they can be the same or different halogens.
  • 2-substituted diethyl malonate is selected from the group consisting of diethyl 2-bromomalonate, diethyl 2,2-dibromomalonate, diethyl 2-chloromalonate, diethyl 2,2-dichloromalonate, and any mixtures thereof.
  • 2-halo-substituted diethyl malonate is a mixture selected from the group consisting of: diethyl 2-bromomalonate and diethyl 2,2- dibromomalonate; diethyl 2-chloromalonate and diethyl 2,2-dichloromalonate; diethyl 2-bromomalonate and diethyl 2-chloromalonate; diethyl 2-bromomalonate and diethyl 2,2-dichloromalonate; diethyl 2,2-dibromomalonate and diethyl 2- chloromalonate; diethyl 2,2-dibromomalonate and diethyl 2,2-dichloromalonate; diethyl 2-bromomalonate and diethyl 2,2-dibromomalonate and diethyl 2- chloromalonate; diethyl 2-bromomalonate and diethyl 2,2-dibromomalonate and diethyl
  • the present invention provides a process for the preparation of 1,3-diethyl 2-(2-methylhydrazinylidene)propanedioate by reacting 2- halo- substituted diethyl malonate with methylhydrazine or the salt thereof in a solvent or without solvent.
  • the solvent is an organic solvent.
  • the solvent is selected from the group consisting of methanol, ethanol, 1-propanol, isopropyl alcohol, acetonitrile and any mixtures thereof.
  • the present invention provides a process for the preparation of 1,3-diethyl 2-(2-methylhydrazinylidene)propanedioate by reacting 2- halo- substituted diethyl malonate with methylhydrazine or the salt thereof in the presence of a catalyst.
  • the catalyst belongs to organic acid group.
  • the catalyst is selected from the group consisting of acetic acid, hydrochloric acid, sulfuric acid, phosphoric acid and any mixtures thereof.
  • the present invention provides a process for the preparation of 1,3-diethyl 2-(2-methylhydrazinylidene)propanedioate by reacting 2- halo- substituted diethyl malonate with methylhydrazine or the salt thereof at the temperature range from about 10 to about 80 0 C. In another embodiment, the process is carried out at the temperature range from about 20 to about 70 0 C.
  • the present invention provides a process for the preparation of 1,3-diethyl 2-(2-methylhydrazinylidene)propanedioate by reacting 2- halo- substituted diethyl malonate with methylhydrazine or the salt thereof in a solvent selected from the group consisting of the methanol, ethanol, 1-propanol, isopropyl alcohol, acetonitrile and any mixtures thereof in the presence of a catalyst selected from the group consisting of acetic acid, hydrochloric acid, sulfuric acid, phosphoric acid and any mixtures at the temperature range from about 10 to about 80 ° C.
  • 2-halo-substituted diethyl malonate is selected from the group consisting of: diethyl 2-bromomalonate, diethyl 2,2-dibromomalonate, diethyl
  • 2-halogenated diethyl malonate is a mixture selected from the group consisting of: diethyl 2-bromomalonate and diethyl 2,2-dibromomalonate; diethyl 2-chloromalonate and diethyl 2,2-dichloromalonate; diethyl 2- bromomalonate and diethyl 2-chloromalonate; diethyl 2-bromomalonate and diethyl
  • the present invention provides a process of the preparation of 1,3-diethyl 2-(2-methylhydrazinylidene)propanedioate by reacting 2-halo- substituted diethyl malonate with methylhydrazine or the salt thereof in a solvent selected from ethanol or acetonitrile in the presence of the catalyst of acetic acid at the temperature range from about 20 to about 80° C. In another embodiment, the reaction temperature range is 20 about to about 70° C. In a further embodiment, the process is carried out by adding 2-halogenated diethyl malonate to methylhydrazine dropwise.
  • the material 2-halogenated malonate can be easily obtained by reacting malonate with the corresponding halogen.
  • the preparation of 2-halogenated malonate is well known to a person skilled in the art and has been described in many previous documents.
  • Organic Syntheses, Volume 7, Page 34 (1972) described a process for the preparation of bromo- malonate by reacting diethyl malonate with bromine.
  • JP27004157(1952) described a process for the preparation of diethyl 2,2-dibromomalonate by reacting diethyl malonate with bromine.
  • chloro- malonate was described for example in Russian Journal of Applied Chemistry (Zhurnal Prikladnoi Khimii) (1985), 58(11), 2504-8, and the patent documents like US2008114196A1 and DE102006053380, where chloro- malonate was prepared by reacting diethyl malonate with chlorine. All these previous disclosures are hereby incorporated by reference in its entirety.

Abstract

A process for the synthesis of the intermediate useful for the preparation of 1,3,4- triazines, are disclosed.

Description

PROCESS FOR THE SYNTHESIS OF INTERMEDIATES USEFUL FOR PREPARING 1,3,4-TRIAZINE DERIVATIVES
TECHNICAL FIELD
[0001] The present invention relates to the synthesis of the intermediates useful for the preparation of 1,3,4- triazine derivatives, more specifically the intermediate is 1 ,3-diethyl 2-(2-methylhydrazinylidene)propanedioate.
BACKGROUND
[0002] 1,3,4- triazine-based derivatives are a subgroup of the triazines and many of them exhibit herbicidal activity and have been synthesized and widely used to protect crop against weeds. More recently, a novel 1,3,4-triazine based derivative was reported by SHIBAYAMA, Atsushi, et al in WO 2012/002096 A.
[0003] 1,3-diethyl 2-(2-methylhydrazinylidene)propanedioate (the "DMP") is an important intermediate compound for the preparation of the 1,3,4- triazine based derivatives and that is used mainly to form the 1,3,4- triazine ring. With respect to the preparation of the DMP, the diethyl malonate is often used as a starting raw material and first converted to diethyl ketomalonate. Then, the resultant diethyl ketomalonate is to react with methylhydrazine to obtain DMP. One shortcoming of this process is the involvement of the conversion from diethyl malonate to diethyl ketomalonate, which by nature is a hazardous oxidation reaction and involves undesired complicated side reactions. Thus, there is still a strong need for the provision of a more efficient and effective process for the preparation of the DMP in avoidance of the stated shortcoming. SUMMARY
[0004] That need is fulfilled by the present invention. The present invention provides a novel process for the synthesis of 1,3-diethyl 2-(2- methylhydrazinylidene)propanedioate. The present process uses 2-halo-substituted diethyl malonate (referred to herein as "-DEM") and does not need convert diethyl malonate to diethyl ketomalonate. Therefore, the unwanted hazardous oxidation and complicated side reaction are avoided.
[0005] In one aspect, the present invention provides a process for the synthesis of 1,3-diethyl 2-(2-methylhydrazinylidene)propanedioate by reacting 2-halo- substituted diethyl malonate with methylhydrazine or the salt thereof. In one embodiment, 2-halo-substituted diethyl malonate is selected from the group consisting of diethyl 2-bromomalonate, diethyl 2,2-dibromomalonate, diethyl 2- chloromalonate, diethyl 2,2-dichloromalonate, and any mixtures thereof.
[0006] In another aspect, the present invention provides a process for the synthesis of 1,3-diethyl 2-(2-methylhydrazinylidene)propanedioate, comprising:
reacting 2-halo-substituted diethyl malonate with methylhydrazine or the salt thereof in a solvent selected from the group consisting of methanol, ethanol, 1-propanol, isopropyl alcohol, acetonitrile and any mixtures thereof in the presence of a catalyst selected from the group consisting of acetic acid, hydrochloric acid, sulfuric acid, phosphoric acid and any mixtures thereof at the temperature range from about 10 to about 80° C. In one embodiment, the process is carried out in the solvent of ethanol in the presence of the catalyst of acetic acid at the temperature range of about 20 to about 70 0 C. DETAILED DESCRIPTION
[0007] The present invention provides a process for the preparation of 1,3-diethyl 2- (2-methylhydrazinylidene)propanedioate by using 2-halo-substituted diethyl malonate.
[0008] In one aspect, the present invention provides a process for the synthesis of 1,3-diethyl 2-(2-methylhydrazinylidene)propanedioate by reacting a 2-halo- substituted diethyl malonate with methylhydrazine or the salt thereof. As used in the context of the present invention, the term "2-halo-substituted diethyl malonate" refers to a halo-substituted diethyl malonate that includes one or two halogen substituent(s) at carbon-2 position of the diethyl malonate. The halo-substituent can be any member of the halogen family, including fluorine, bromine, chlorine, iodine and combinations thereof. In case of two halogen substituent, they can be the same or different halogens.
[0009] In one embodiment, 2-substituted diethyl malonate is selected from the group consisting of diethyl 2-bromomalonate, diethyl 2,2-dibromomalonate, diethyl 2-chloromalonate, diethyl 2,2-dichloromalonate, and any mixtures thereof.
[0010] In another embodiment, 2-halo-substituted diethyl malonate is a mixture selected from the group consisting of: diethyl 2-bromomalonate and diethyl 2,2- dibromomalonate; diethyl 2-chloromalonate and diethyl 2,2-dichloromalonate; diethyl 2-bromomalonate and diethyl 2-chloromalonate; diethyl 2-bromomalonate and diethyl 2,2-dichloromalonate; diethyl 2,2-dibromomalonate and diethyl 2- chloromalonate; diethyl 2,2-dibromomalonate and diethyl 2,2-dichloromalonate; diethyl 2-bromomalonate and diethyl 2,2-dibromomalonate and diethyl 2- chloromalonate; diethyl 2-bromomalonate and diethyl 2,2-dibromomalonate and diethyl 2,2-dichloromalonate; diethyl 2-bromomalonate and diethyl 2- chloromalonate and diethyl 2,2-dichloromalonate; diethyl 2,2-dibromomalonate and diethyl 2-chloromalonate and diethyl 2,2-dichloromalonate; diethyl 2- bromomalonate and diethyl 2,2-dibromomalonate and diethyl 2-chloromalonate and diethyl 2,2-dichloromalonate.
[0011] In another aspect, the present invention provides a process for the preparation of 1,3-diethyl 2-(2-methylhydrazinylidene)propanedioate by reacting 2- halo- substituted diethyl malonate with methylhydrazine or the salt thereof in a solvent or without solvent. In one embodiment, the solvent is an organic solvent. In a further embodiment, the solvent is selected from the group consisting of methanol, ethanol, 1-propanol, isopropyl alcohol, acetonitrile and any mixtures thereof.
[0012] In another aspect, the present invention provides a process for the preparation of 1,3-diethyl 2-(2-methylhydrazinylidene)propanedioate by reacting 2- halo- substituted diethyl malonate with methylhydrazine or the salt thereof in the presence of a catalyst. In one embodiment, the catalyst belongs to organic acid group. In a further embodiment, the catalyst is selected from the group consisting of acetic acid, hydrochloric acid, sulfuric acid, phosphoric acid and any mixtures thereof. [0013] In another aspect, the present invention provides a process for the preparation of 1,3-diethyl 2-(2-methylhydrazinylidene)propanedioate by reacting 2- halo- substituted diethyl malonate with methylhydrazine or the salt thereof at the temperature range from about 10 to about 80 0 C. In another embodiment, the process is carried out at the temperature range from about 20 to about 70 0 C.
[0014] In another aspect, the present invention provides a process for the preparation of 1,3-diethyl 2-(2-methylhydrazinylidene)propanedioate by reacting 2- halo- substituted diethyl malonate with methylhydrazine or the salt thereof in a solvent selected from the group consisting of the methanol, ethanol, 1-propanol, isopropyl alcohol, acetonitrile and any mixtures thereof in the presence of a catalyst selected from the group consisting of acetic acid, hydrochloric acid, sulfuric acid, phosphoric acid and any mixtures at the temperature range from about 10 to about 80 ° C.
[0015] In one embodiment, 2-halo-substituted diethyl malonate is selected from the group consisting of: diethyl 2-bromomalonate, diethyl 2,2-dibromomalonate, diethyl
2-chloromalonate and diethyl 2,2-dichloromalonate, and any mixtures thereof. In a further embodiment, 2-halogenated diethyl malonate is a mixture selected from the group consisting of: diethyl 2-bromomalonate and diethyl 2,2-dibromomalonate; diethyl 2-chloromalonate and diethyl 2,2-dichloromalonate; diethyl 2- bromomalonate and diethyl 2-chloromalonate; diethyl 2-bromomalonate and diethyl
2,2-dichloromalonate; diethyl 2,2-dibromomalonate and diethyl 2-chloromalonate; diethyl 2,2-dibromomalonate and diethyl 2,2-dichloromalonate; diethyl 2- bromomalonate and diethyl 2,2-dibromomalonate and diethyl 2-chloromalonate; diethyl 2-bromomalonate and diethyl 2,2-dibromomalonate and diethyl 2,2- dichloromalonate; diethyl 2-bromomalonate and diethyl 2-chloromalonate and diethyl 2,2-dichloromalonate; diethyl 2,2-dibromomalonate and diethyl 2- chloromalonate and diethyl 2,2-dichloromalonate; diethyl 2-bromomalonate and diethyl 2,2-dibromomalonate and diethyl 2-chloromalonate and diethyl 2,2- dichloromalonate. In another embodiment, the process is carried out in the solvent of ethanol or acetonitrile in the presence of the catalyst of acetic acid at the temperature range from about 20 to about 70 0 C.
[0016] In another aspect, the present invention provides a process of the preparation of 1,3-diethyl 2-(2-methylhydrazinylidene)propanedioate by reacting 2-halo- substituted diethyl malonate with methylhydrazine or the salt thereof in a solvent selected from ethanol or acetonitrile in the presence of the catalyst of acetic acid at the temperature range from about 20 to about 80° C. In another embodiment, the reaction temperature range is 20 about to about 70° C. In a further embodiment, the process is carried out by adding 2-halogenated diethyl malonate to methylhydrazine dropwise.
[0017] The material 2-halogenated malonate can be easily obtained by reacting malonate with the corresponding halogen. The preparation of 2-halogenated malonate is well known to a person skilled in the art and has been described in many previous documents. For example, Organic Syntheses, Volume 7, Page 34 (1972) described a process for the preparation of bromo- malonate by reacting diethyl malonate with bromine. JP27004157(1952) described a process for the preparation of diethyl 2,2-dibromomalonate by reacting diethyl malonate with bromine. The preparation of chloro- malonate was described for example in Russian Journal of Applied Chemistry (Zhurnal Prikladnoi Khimii) (1985), 58(11), 2504-8, and the patent documents like US2008114196A1 and DE102006053380, where chloro- malonate was prepared by reacting diethyl malonate with chlorine. All these previous disclosures are hereby incorporated by reference in its entirety.
[0018] The present invention is further illustrated by the following examples. These examples serve merely to illustrate particular embodiments of the invention and are not intended to limit the scope of the invention in any way. Further modifications encompassed by the disclosed invention will be apparent to those skilled in the art. All such modifications are deemed to be within the scope of the invention as defined in the present specification and claims.
EXAMPLES
Example 1 - Preparation of DMP using Cl-DEM
Cl-DEM
[0019] 9.9 g of diethyl 2-chloromalonate was dissolved in 50 g of acetonitrile. The reaction solution was heated to 60° C. 13.3 g of 41% methylhydrazine was added into the solution drop-wise at 60°C during-reflux. The reaction was monitored by gas chromatography (the "GC"). After the reaction was completed (the remained diethyl 2-chloromalonate in the reaction <1%, determined by gas chromatography) in 4 hours, water and toluene was added to extract the product. The toluene phase was concentrated to give 8.3 g of diethyl 2-(2-methylhydrazono)malonate as an oil. The purity is 71.3%. The yield is 58.6%.
Example 2 - Preparation of DMP using diBr-DEM
diBr-DEM
[0020] 13.6 g of 41% methylhydrazine was dissolved in 13.6 g of ethanol. 13.2 g of diethyl 2,2-dibromomalonate was added into the solution drop-wise at 20-40° C. The reaction was monitored by GC. After the reaction was completed (the remained diethyl 2,2-dibromomalonate in the reaction < 1%, determined by gas
chromatography) in 6 hours, water and toluene was added to extract the product. The toluene phase was concentrated to give 7.7 g of diethyl 2-(2- methylhydrazono)malonate as an oil. The purity is 81.6%. The yield is 77.7%.
Example 3 - Preparation of DMP using Br-DEM
Br-DEJW [0021] 11 g of 41% methylhydrazine was dissolved in a mixture of 30 g of ethanol and 1.2 g of acetic acid. 10 g of diethyl 2-bromomalonate was added into the solution dropwise at 50-60° C. The reaction was monitored by GC. After the reaction was completed (diethyl 2-bromomalonate < 1%, determined by gas chromatography) in 2 hours, water and toluene was added to extract the product. The toluene phase was concentrated to give 8.5 g of diethyl 2-(2- methylhydrazono)malonate as an oil. The purity is 74.5%. The yield is 78.9%.
Example 4 - Preparation of DMP using the Mixture of Br-DEM and diBr-DEM
Br-DEM diBr-DEM
34% 66%
[0022] 11.3 g of 41% methylhydrazine was dissolved in a mixture of 15 g of ethanol and 1.0 g of acetic acid. 9.7 g mixture of diethyl 2-bromomalonate (34%) and diethyl 2,2-dibromomalonate (66%) was added into the solution dropwise at 58- 70° C. The reaction was monitored by GC. After the reaction was completed (diethyl 2-bromomalonate < 1%, determined by gas chromatography) in 1 hour, water and toluene was added to extract the product. The toluene phase was concentrated to give 6.8 g of diethyl 2-(2-methylhydrazono)malonate as an oil. The purity is 75.05%. The yield is 75.5%. [0023] While this invention has been described with an emphasis upon preferred embodiments, it will be obvious to those of ordinary skill in the art that variations in the preferred compositions and methods can be used and that it is intended that the invention can be practiced otherwise than as specifically described herein.
Accordingly, this invention includes all modifications encompassed within the spirit and scope of the invention as defined by the claims that follow.

Claims

CLAIMS What is claimed is:
1. A process for the preparation of 1,3-diethyl 2-(2- methylhydrazinylidene)propanedioate, comprising: reacting 2- halosubstituted diethyl malonate with methylhydrazine or the salt thereof.
2. A process according to Claim 1, wherein the 2-halo-substituted diethyl malonate is selected from the group consisting of diethyl -2-bromomalonate, diethyl -2,2-dibromomalonate, diethyl- 2-chloromalonate, diethyl -2,2- dichloromalonate, and any mixtures thereof.
3. A process according to Claim 1, wherein 2-halo-substituted diethyl malonate is a mixture selected from the group consisting of: diethyl- 2- bromomalonate and diethyl 2,2-dibromomalonate; diethyl- 2-chloromalonate and diethyl- 2,2-dichloromalonate; diethyl- 2-bromomalonate and diethyl- 2- chloromalonate; diethyl- 2-bromomalonate and diethyl- 2,2- dichloromalonate; diethyl- 2,2-dibromomalonate and diethyl- 2- chloromalonate; diethyl- 2,2-dibromomalonate and diethyl- 2,2- dichloromalonate; diethyl -2-bromomalonate and diethyl- 2,2- dibromomalonate and diethyl- 2-chloromalonate; diethyl- 2-bromomalonate and diethyl- 2,2-dibromomalonate and diethyl- 2,2-dichloromalonate;
diethyl- 2-bromomalonate and diethyl- 2-chloromalonate and diethyl- 2,2- dichloromalonate; diethyl -2,2-dibromomalonate and diethyl- 2- chloromalonate and diethyl- 2,2-dichloromalonate; diethyl- 2- bromomalonate and diethyl- 2,2-dibromomalonate and diethyl- 2- chloromalonate and diethyl- 2,2-dichloromalonate.
4. A process according to Claim 1, wherein the process is carried out in a solvent selected from the group consisting of: methanol, ethanol, 1-propanol, isopropyl alcohol, acetonitrile and any mixtures thereof.
5. A process according to Claim 1, wherein the process is carried out in the presence of a catalyst, preferably selected from the group consisting of: acetic acid, hydrochloric acid, sulfuric acid, phosphoric acid, and any mixtures thereof.
6. A process according to Claim 1, wherein the process in carried out at the temperature range from about 10 to about 80° C, preferably from about 20 to about 70° C.
7. A process for the preparation of 1,3-diethyl 2-(2- methylhydrazinylidene)propanedioate, comprising: reacting 2-halo- substituted diethyl malonate with methylhydrazine or the salt thereof in a solvent selected from the group consisting of: methanol, ethanol, 1-propanol, isopropyl alcohol, acetonitrile and any mixtures thereof, in the presence of a catalyst selected from the group consisting of acetic acid, hydrochloric acid, sulfuric acid, phosphoric acid and any mixtures thereof, and at a temperature ranging from about 10 to about 80° C.
8. A process according to Claim 7, wherein the process is carried out in ethanol in the presence of acetic acid at the temperature range of from about 20 to about 70° C.
9. A process according to Claim 7, wherein 2-halo-substituted diethyl malonate is a mixture selected from the group consisting of: diethyl- 2- bromomalonate and diethyl 2,2-dibromomalonate; diethyl- 2-chloromalonate and diethyl- 2,2-dichloromalonate; diethyl- 2-bromomalonate and diethyl- 2- chloromalonate; diethyl- 2-bromomalonate and diethyl- 2,2- dichloromalonate; diethyl 2,2-dibromomalonate and diethyl 2- chloromalonate; diethyl- 2,2-dibromomalonate and diethyl- 2,2- dichloromalonate; diethyl- 2-bromomalonate and diethyl- 2,2- dibromomalonate and diethyl- 2-chloromalonate; diethyl- 2-bromomalonate and diethyl- 2,2-dibromomalonate and diethyl- 2,2-dichloromalonate;
diethyl- 2-bromomalonate and diethyl- 2-chloromalonate and diethyl- 2,2- dichloromalonate; diethyl- 2,2-dibromomalonate and diethyl- 2- chloromalonate and diethyl- 2,2-dichloromalonate; diethyl- 2- bromomalonate and diethyl- 2,2-dibromomalonate and diethyl- 2- chloromalonate and diethyl- 2,2-dichloromalonate.
10. A process according to Claim 7, wherein the process is carried out by adding 2-halo-substituted diethyl malonate to methylhydrazine dropwise.
EP16866914.1A 2015-11-18 2016-11-14 Process for the synthesis of intermediates useful for preparing 1,3,4-triazine derivatives Not-in-force EP3377470B1 (en)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CH652709A5 (en) 1983-01-06 1985-11-29 Lonza Ag METHOD FOR PRODUCING ESTERS OF MESOXAL ACID.
IT1175533B (en) 1984-06-20 1987-07-01 Montedison Spa PROCESS FOR THE PREPARATION OF CARBONYL COMPOUNDS
IT1233862B (en) 1988-02-24 1992-04-21 Mini Ricerca Scient Tecnolog CATALYTIC PROCESS FOR THE SYNTHESIS OF ETHYLENTETRACARBOSSYLIC ACID ESTERS.
US5273975A (en) * 1989-06-09 1993-12-28 The Upjohn Company Heterocyclic amines having central nervous system activity
DE4309900C1 (en) * 1993-03-26 1994-06-30 Goldschmidt Ag Th Process for the preparation of amphoteric surfactants
TWI441637B (en) * 2005-05-18 2014-06-21 Array Biopharma Inc Heterocyclic inhibitors of mek and methods of use thereof
DE102006053380A1 (en) 2006-11-13 2008-05-15 Wacker Chemie Ag Chlorinated or partly chlorinated carbonyl compound production for use in pharma and agro industry, involves introducing unchlorinated or partly chlorinated carbonyl compound in jet loop reactor
WO2008120004A1 (en) * 2007-04-02 2008-10-09 Astrazeneca Ab Combination of a mek- inhibitor and a b-raf inhibitor for the treatment of cancer
BRPI0818426A2 (en) * 2007-10-15 2017-06-13 Astrazeneca Ab combination product, use of a combination product, and method for treating cancer
KR101738491B1 (en) 2009-06-26 2017-05-22 이하라케미칼 고교가부시키가이샤 Process for production of ketomalonic acid compounds or hydrates thereof
WO2011095807A1 (en) * 2010-02-07 2011-08-11 Astrazeneca Ab Combinations of mek and hh inhibitors
NZ602800A (en) 2010-06-29 2014-12-24 Kumiai Chemical Industry Co 6-acyl-1,2,4-triazine-3,5-dione derivative and herbicides
WO2014031971A1 (en) 2012-08-24 2014-02-27 E. I. Du Pont De Nemours And Company Herbicidal pyridazinones
GB201403495D0 (en) * 2014-02-27 2014-04-16 Syngenta Participations Ag Improvements in or relating to organic compounds

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